Autosomal dominant polycystic kidney disease (ADPKD) affects millions of people and it is the fourth leading cause of kidney failure in the United States. The two genes encoded in this disease are PKD1 and PKD2, and mutations in either gene are associated with the phoenotype seen in ADPKD. The long-term objective entails PKD2 gene product, polycystin-2, functions as a calcium permeable nonselective cation channel. Dysregulation of this channel provides mechanism for the onset and progression of ADPKD. The specific aims of this research include to (1) Determine the interaction between polycystin-2 and the ryanodine receptor (RYR); (2) What effects mutated variants of polycystin-2 would impact on the function of polycystin-2; (3) Develop a screening assay for putative agonists and antagonists of PKD2. Since these channels are intracellular calcium channels, planar lipid bilayer and calcium imaging techniques will be used to perform this study.